There is considerable confusion regarding outcome from randomised controlled trials (RCT) using fibrates.Even after more than 20 years of widespread use of fibrates we are still dealing with uncertainty.We have made the following observations based on patients seen in the metabolic clinics at the Heart of England Foundation Trust in Birmingham, UK.Fibrates and changes observed in HDL-C: We have analysed results from 248 patients treated with fibrates and the mean increase in HDL-C was a significant, but modest 0.059 mmol/l.HDL-C change was associated with baseline HDL-C levels, diabetes and duration of fibrate treatment.When all these factors were entered into the model they appeared independent retaining statistical significance.Patients with a baseline HDL-C<1.0 mmol/l showed a significantly greater HDL-C increase (0.15 mmol/l) than patients with a HDL-C≥1.0 mmol/l (0.002 mmol/l).This relationship was seen in all patient groups apart from females and those on concurrent statin treatment.Paradoxical decrease in HDL-C following lipid lowering treatment: We have over 20 patients demonstrating this pattern with a greater than 50% decrease in HDL-C, and will show variation within the group including fibrate monotherapy, glitazones when added to a fibrate and a patient on statins.Changes in creatinine and liver function tests following fibrate treatment: Creatinine increased significantly (paired t test, p=0.001) from a mean of 81.9μmol/l to 93.8 μmol/l and this was seen in all patient subgroups.Males, those with lower baseline creatinine levels, diabetics were associated with greater creatinine increase in independent linear regression models.There was an inverse relationship between triglycerides reduction and the increase in creatinine levels.We have also shown that improvements in liver function tests are associated with fibrates.This change was dependent on the degree of abnormality pre-treatment with higher baseline abnormalities resulting in greater improvement.